NCT_ID: NCT05753930
Clinical Trial Link
Brief Summaries
Sequence: | 30856319 |
Description | The goal of this clinical trial is to learn about the efficacy and safety of imlifidase in highly sensitized paediatric patients, 1-17 years old, with end stage renal disease (ESRD). The main questions it aims to answer are: Does imlifidase treatment result in crossmatch conversion that enables transplantation? How is the function of the transplanted kidney? The participants will be hospitalised in accordance with the normal routines for transplanted patients. The patients will receive medication to prevent rejection of the donor kidney, and because such treatment make the body more vulnerable medications to prevent infections. |
Studies
Study First Submitted Date | 2023-02-23 |
Study First Posted Date | 2023-03-03 |
Last Update Posted Date | 2023-07-07 |
Start Month Year | June 2, 2023 |
Primary Completion Month Year | September 30, 2024 |
Verification Month Year | July 2023 |
Verification Date | 2023-07-31 |
Last Update Posted Date | 2023-07-07 |
Detailed Descriptions
Sequence: | 20782209 |
Description | After being informed about the study and potential risks, all patients giving written informed consent will undergo pre-screening to determine eligibility for study entry. The trial will include highly sensitised ESRD paediatric patients (1-17 years). The patients have previously undergone desensitization unsuccessfully or have an anti-HLA antibody status deemed too difficult to make a successful desensitization using other experimental methods. A screening visit will take place when an organ offer has been placed for a final check of the patients' eligibility for study participation. All patients included in the trial will be desensitized with imlifidase to convert the positive XM to negative and then transplanted with either a kidney from a deceased donor (DD) or a living donor (LD). Patients will be hospitalised in accordance with the normal routines for transplanted patients at each clinic. Following transplantation, the patients will receive induction therapies, rejection prophylaxis, and maintenance immunosuppressive therapies. The patients will be closely monitored for any signs of antibody-mediated rejections (AMRs). The duration of the interventional trial period after an organ has been offered will be 6 months for each patient. The trial includes a follow-up part to collect long-term efficacy and safety data up to 5 years after the transplantation. |
Facilities
Sequence: | 200605493 |
Status | Recruiting |
Name | Hospital Unviersitari Vall d'Hebron, Nefrología Pediátrica |
City | Barcelona |
Zip | 08035 |
Country | Spain |
Facility Contacts
Sequence: | 28184934 |
Facility Id | 200605493 |
Contact Type | primary |
Name | Gema Ariceta, MD |
gema.ariceta@vallhebron.cat | |
Facility Investigators
Sequence: | 18379032 |
Facility Id | 200605493 |
Role | Principal Investigator |
Name | Gema Ariceta, MD |
Conditions
Sequence: | 52326036 |
Name | Kidney Transplantation in Highly Sensitized Patients |
Downcase Name | kidney transplantation in highly sensitized patients |
Id Information
Sequence: | 40269373 | Sequence: | 40269374 |
Id Source | org_study_id | Id Source | secondary_id |
Id Value | 20-HMedIdes-21 | Id Value | 2022-500230-28-00 |
Id Type | Other Identifier | ||
Id Type Description | EU Trial Number | ||
Countries
Sequence: | 42688771 |
Name | Spain |
Removed | False |
Design Groups
Sequence: | 55765649 |
Group Type | Experimental |
Title | Imlifidase |
Description | Imlifidase is administered intravenously as one infusion of 0.25 mg/kg over 15 minutes within 24 hours prior to transplantation. |
Interventions
Sequence: | 52637007 |
Intervention Type | Drug |
Name | Imlifidase |
Description | Imlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly selective towards IgG. The cleavage of IgG generates one F(ab')2- and one homodimeric Fc-fragment and efficiently neutralizes Fc-mediated activities of IgG. |
Keywords
Sequence: | 80082231 | Sequence: | 80082222 | Sequence: | 80082223 | Sequence: | 80082224 | Sequence: | 80082225 | Sequence: | 80082226 | Sequence: | 80082227 | Sequence: | 80082228 | Sequence: | 80082229 | Sequence: | 80082230 | Sequence: | 80082232 |
Name | Children | Name | Desensitization | Name | Highly sensitized | Name | Positive crossmatch | Name | Unlikely to be transplanted | Name | Kidney transplantation | Name | Deceased donor | Name | Living donor | Name | End-Stage Renal Disease | Name | Paediatric patients | Name | Incompatible transplant |
Downcase Name | children | Downcase Name | desensitization | Downcase Name | highly sensitized | Downcase Name | positive crossmatch | Downcase Name | unlikely to be transplanted | Downcase Name | kidney transplantation | Downcase Name | deceased donor | Downcase Name | living donor | Downcase Name | end-stage renal disease | Downcase Name | paediatric patients | Downcase Name | incompatible transplant |
Design Outcomes
Sequence: | 177951111 | Sequence: | 177951112 | Sequence: | 177951113 | Sequence: | 177951114 | Sequence: | 177951115 | Sequence: | 177951116 | Sequence: | 177951117 | Sequence: | 177951118 | Sequence: | 177951119 | Sequence: | 177951120 | Sequence: | 177951121 | Sequence: | 177951122 | Sequence: | 177951123 | Sequence: | 177951124 | Sequence: | 177951125 | Sequence: | 177951126 | Sequence: | 177951127 | Sequence: | 177951128 | Sequence: | 177951129 | Sequence: | 177951130 | Sequence: | 177951131 | Sequence: | 177951132 | Sequence: | 177951133 | Sequence: | 177951134 |
Outcome Type | primary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | secondary | Outcome Type | other | Outcome Type | other |
Measure | Proportion of patients with conversion of a positive crossmatch test to negative within 24 hours after start of imlifidase treatment | Measure | Renal function up to 5 years after transplantation as assessed by estimated glomerular filtration rate (eGFR) | Measure | Renal function up to 5 years after transplantation as assessed by serum/plasma creatinine levels | Measure | Renal function up to 5 years after transplantation as assessed by serum/plasma cystatin C levels | Measure | Renal function up to 5 years after transplantation as assessed by proteinuria | Measure | DSA levels up to 5 years after transplantation | Measure | Graft survival (death censored) up to 5 year after transplantation | Measure | Graft failure-free survival up to 5 years after transplantation | Measure | Patient survival up to 5 years after transplantation | Measure | Frequency of delayed graft function (DGF) | Measure | Length of DGF | Measure | Proportion of patients with dialysis dependency up to 5 years after transplantation | Measure | Imlifidase Pharmacokinetics (AUC) | Measure | Imlifidase Pharmacokinetics (Cmax) | Measure | Imlifidase Pharmacokinetics (tmax) | Measure | Imlifidase Pharmacokinetics (t1/2) | Measure | Imlifidase Pharmacokinetics (CL) | Measure | Imlifidase Pharmacokinetics (Vz) | Measure | Imlifidase Pharmacodynamic (PD) profile up to 9 days after imlifidase treatment | Measure | Immunogenicity profile of imlifidase up to 5 years after imlifidase treatment | Measure | Proportion of patients with biopsy- and serology (DSA)-confirmed AMR up to 5 years after transplantation | Measure | Proportion of patients with biopsy confirmed cell-mediated rejection (CMR) up to 5 years after transplantation | Measure | Safety assessed as proportion of patients with infusion related reactions within 48 hours of imlifidase infusion | Measure | Safety assessed as proportion of patients severe or serious infections within 30 days after imlifidase treatment |
Time Frame | From start of imlifidase administration to 24 hours | Time Frame | From pre-dose imlifidase up to 5 years | Time Frame | From pre-dose imlifidase up to 5 years | Time Frame | From pre-dose imlifidase up to 5 years | Time Frame | From pre-dose imlifidase up to 5 years | Time Frame | From pre-dose imlifidase up to 5 years | Time Frame | From 6 months up to 5 years | Time Frame | From 6 months up to 5 years | Time Frame | From 6 months up to 5 years | Time Frame | From transplantation up 7 days after transplantation | Time Frame | From transplantation up 7 days after transplantation | Time Frame | From 6 months up to 5 years | Time Frame | From pre-dose imlifidase up to Day 15 | Time Frame | From pre-dose imlifidase up to Day 15 | Time Frame | From pre-dose imlifidase up to Day 15 | Time Frame | From pre-dose imlifidase up to Day 15 | Time Frame | From pre-dose imlifidase up to Day 15 | Time Frame | From pre-dose imlifidase up to Day 15 | Time Frame | From pre-dose imlifidase up to Day 10 | Time Frame | From pre-dose imlifidase up to 5 years | Time Frame | From transplantation up to 5 years | Time Frame | From transplantation up to 5 years | Time Frame | From start of imlifidase infusion up to 48 hours | Time Frame | From start of imlifidase infusion up to 30 days |
Description | Immunoglobulins (IgG) including donor specific antibodies (DSAs) are rapidly and efficiently cleaved by imlifidase. A conversion of a positive to a negative XM will enable transplantation. | Description | eGFR is a measure of kidney function. Reduced kidney function is characterised by a decreased eGFR value. | Description | Creatinine is a measure of kidney function. Reduced kidney function is characterised by an increased value. | Description | Cystatin C is a measure of kidney function. Reduced kidney function is characterised by an increased value. | Description | Proteinuria (protein/creatinine ratio in urine) is a measure of kidney function. Reduced kidney function is characterised by an increased value. | Description | Donor specific antibodies (DSAs) are antibodies in the recipient directed against the transplanted organ. | Description | DGF is defined as 'Need for dialysis within 7 days of transplantation' in "Delayed graft function in kidney transplantation: developing drugs for prevention, guidance for industry", FDA 2019. Frequency of patients having DGF in accordance with this definition will be presented. | Description | DGF is defined as 'Need for dialysis within 7 days of transplantation' in "Delayed graft function in kidney transplantation: developing drugs for prevention, guidance for industry", FDA 2019. The duration of DGFs in accordance with this definition will be presented. | Description | AUC = Area under the imlifidase plasma concentration versus time curve. | Description | Cmax = Maximum observed plasma concentration of imlifidase following dosing. | Description | tmax = Time point for maximum observed plasma concentration of imlifidase following dosing | Description | t1/2 = Terminal half-life of imlifidase. | Description | CL = Clearance of imlifidase. | Description | Vz = Volume of distribution during the elimination phase | Description | PD is assessed as serum concentrations of intact IgG and its fractions following infusion. | Description | Immunogenicity is assessed as serum concentration of anti-imlifidase IgG (ADA). | Description | Banff scores (Loupy et al. 2020) will be used for biopsy evaluation. | Description | Banff scores (Loupy et al. 2020) will be used for biopsy evaluation. |
Sponsors
Sequence: | 48464375 |
Agency Class | INDUSTRY |
Lead Or Collaborator | lead |
Name | Hansa Biopharma AB |
Overall Officials
Sequence: | 29367717 |
Role | Study Director |
Name | Clinical Operations |
Affiliation | Hansa Biopharma AB |
Central Contacts
Sequence: | 12047472 |
Contact Type | primary |
Name | Central Contact |
Phone | +46 46 16 56 70 |
clinicalstudyinfo@hansabiopharma.com | |
Role | Contact |
Design Group Interventions
Sequence: | 68358345 |
Design Group Id | 55765649 |
Intervention Id | 52637007 |
Eligibilities
Sequence: | 30855100 |
Gender | All |
Minimum Age | 1 Year |
Maximum Age | 17 Years |
Healthy Volunteers | No |
Criteria | Inclusion Criteria: Signed Informed Consent obtained from patient/parent/legal guardian/independent witness (depending on patient's age) before any trial-related procedures Highly sensitised patient with panel reactive antibodies (PRA) ≥80% Male or female patient between the age of 1 to 17 years (up to the day before the 18th birthday) at the time of screening Patient with end-stage renal disease (ESRD) and waiting for a renal transplant from a living or deceased donor Patient must be transplantable (including size mismatch) at the time of obtaining informed consent for trial participation Patients who have previously undergone desensitisation unsuccessfully with plasmapheresis/IVIg/anti-CD20 or have an anti-HLA antibody status deemed too difficult to make a successful desensitisation (judgement based on physicians' previous experience with similar patients) Positive crossmatch (XM) test determined by flow cytometry crossmatch (FCXM) and/or complement-dependent cytotoxicity crossmatch (CDCXM) tests against the donor. For the DD patients, if physical XM tests are not practically possible due to lack of time, patients may be included on a virtual crossmatch (vXM) predictive of a positive XM test. Willingness and ability to comply with the protocol as judged by the investigator Exclusion Criteria: Previous treatment with imlifidase IVIg treatment within 28 days prior to imlifidase treatment Desensitisation treatment(s) within 1 month prior to the current transplantation Hypersensitivity to the active substance (imlifidase) or to any of the excipients and to other immunosuppressive drugs specified in the protocol Ongoing serious infections Present, or history of, thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP At the time of transplantation: severe other condition requiring treatment and close monitoring e.g. cardiac failure ≥ grade 4 (New York Heart Association), unstable coronary disease, active peripheral vascular disease, proven hypercoagulable conditions/events or oxygen dependent respiratory disease Malignancy within 3 years prior to transplantation ABO blood group incompatible transplantations (A2 and A2B kidneys will not be accepted for B recipients) Any other reason that, in the view of the investigator, precludes transplantation Breast feeding or pregnancy, if applicable Woman of fertile age and sexually active without adequate contraceptive measures to avoid pregnancy during the interventional trial period (i.e. up to 6 months after transplantation) Suspicion of Covid-19 infection or positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test Positive serology for human immunodeficiency virus (HIV) Clinical signs of hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), or Epstein Barr virus (EBV) infection Donor with positive serology for HIV, HBV, HCV, CMV or EBV to a patient with negative serology (mismatch serology) Clinically relevant active infection(s) as judged by the investigator Tuberculosis Use of other investigational agents within 5 terminal elimination half-lives prior to the transplantation Contemporaneous participation in medical device studies Known mental incapacity or language barriers precluding patients'/parents'/legal guardians' adequate understanding of the informed consent information and the trial activities Inability by the judgement of the investigator to participate in the trial for any other reason |
Adult | False |
Child | True |
Older Adult | False |
Calculated Values
Sequence: | 254311605 |
Number Of Facilities | 1 |
Registered In Calendar Year | 2023 |
Were Results Reported | False |
Has Us Facility | False |
Has Single Facility | True |
Minimum Age Num | 1 |
Maximum Age Num | 17 |
Minimum Age Unit | Year |
Maximum Age Unit | Years |
Number Of Primary Outcomes To Measure | 1 |
Number Of Secondary Outcomes To Measure | 21 |
Number Of Other Outcomes To Measure | 2 |
Designs
Sequence: | 30600942 |
Allocation | N/A |
Intervention Model | Single Group Assignment |
Observational Model | |
Primary Purpose | Treatment |
Time Perspective | |
Masking | None (Open Label) |
Intervention Model Description | This is an open-label, non-randomised trial in highly sensitized paediatric kidney transplant patients with positive XM against an available DD or LD. The rationale for a non-randomised trial in DD kidney transplantation is that there are no other effective or approved desensitisation protocols that would provide a suitable or ethical control. The rationale for a non-randomised trial in LD kidney transplantation is that potential control treatments have already been tried unsuccessfully in the patients or such treatments are judged as highly unlikely to succeed based on the breadth and depth of the patients' sensitisation. Treatment with little anticipation of success would expose the patients to unnecessary immunosuppression. |
Intervention Other Names
Sequence: | 26746575 |
Intervention Id | 52637007 |
Name | IdeS, HMED-IdeS |
Responsible Parties
Sequence: | 28967451 |
Responsible Party Type | Sponsor |
Study References
Sequence: | 52230820 |
Pmid | 32463180 |
Reference Type | background |
Citation | Loupy A, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M, Akalin E, Alachkar N, Bagnasco S, Becker JU, Cornell LD, Clahsen-van Groningen MC, Demetris AJ, Dragun D, Duong van Huyen JP, Farris AB, Fogo AB, Gibson IW, Glotz D, Gueguen J, Kikic Z, Kozakowski N, Kraus E, Lefaucheur C, Liapis H, Mannon RB, Montgomery RA, Nankivell BJ, Nickeleit V, Nickerson P, Rabant M, Racusen L, Randhawa P, Robin B, Rosales IA, Sapir-Pichhadze R, Schinstock CA, Seron D, Singh HK, Smith RN, Stegall MD, Zeevi A, Solez K, Colvin RB, Mengel M. The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection. Am J Transplant. 2020 Sep;20(9):2318-2331. doi: 10.1111/ajt.15898. Epub 2020 May 28. |